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Involvement of Essential Signaling Cascades and Analysis of Gene Networks in Diabesity

1
School of BioSciences and Technology, Vellore Institute of Technology, Vellore 632014, Tamil Nadu, India
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School of Computer Science and Engineering, Vellore Institute of Technology, Vellore 632014, Tamil Nadu, India
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Department of Biomedical Sciences, College of Health and Sciences, QU Health, Qatar University, Doha 2713, Qatar
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Department of Genetic Engineering, Kattankulathur Campus, SRM Institute of Science and Technology, Chennai 603203, Tamil Nadu, India
*
Authors to whom correspondence should be addressed.
Genes 2020, 11(11), 1256; https://doi.org/10.3390/genes11111256
Received: 21 September 2020 / Revised: 17 October 2020 / Accepted: 22 October 2020 / Published: 25 October 2020
(This article belongs to the Section Molecular Genetics and Genomics)
(1) Aims: Diabesity, defined as diabetes occurring in the context of obesity, is a serious health problem that is associated with an increased risk of premature heart attack, stroke, and death. To date, a key challenge has been to understand the molecular pathways that play significant roles in diabesity. In this study, we aimed to investigate the genetic links between diabetes and obesity in diabetic individuals and highlight the role(s) of shared genes in individuals with diabesity. (2) Methods: The interactions between the genes were analyzed using the Search Tool for the Retrieval of Interacting Genes (STRING) tool after the compilation of obesity genes associated with type 1 diabetes (T1D), type 2 diabetes (T2D), and maturity-onset diabetes of the young (MODY). Cytoscape plugins were utilized for enrichment analysis. (3) Results: We identified 546 obesity genes that are associated with T1D, T2D, and MODY. The network backbone of the identified genes comprised 514 nodes and 4126 edges with an estimated clustering coefficient of 0.242. The Molecular Complex Detection (MCODE) generated three clusters with a score of 33.61, 16.788, and 6.783, each. The highest-scoring nodes of the clusters were AGT, FGB, and LDLR genes. The genes from cluster 1 were enriched in FOXO-mediated transcription of oxidative stress, renin secretion, and regulation of lipolysis in adipocytes. The cluster 2 genes enriched in Src homology 2 domain-containing (SHC)-related events triggered by IGF1R, regulation of lipolysis in adipocytes, and GRB2: SOS produce a link to mitogen-activated protein kinase (MAPK) signaling for integrins. The cluster 3 genes ere enriched in IGF1R signaling cascade and insulin signaling pathway. (4) Conclusion: This study presents a platform to discover potential targets for diabesity treatment and helps in understanding the molecular mechanism. View Full-Text
Keywords: diabetes; T2D; T1D; MODY; obesity; diabesity; protein-protein interaction diabetes; T2D; T1D; MODY; obesity; diabesity; protein-protein interaction
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MDPI and ACS Style

S., U.K.; Rajan, B.; D., T.K.; V., A.P.; Abunada, T.; Younes, S.; Okashah, S.; Ethiraj, S.; C., G.P.D.; Zayed, H. Involvement of Essential Signaling Cascades and Analysis of Gene Networks in Diabesity. Genes 2020, 11, 1256. https://doi.org/10.3390/genes11111256

AMA Style

S. UK, Rajan B, D. TK, V. AP, Abunada T, Younes S, Okashah S, Ethiraj S, C. GPD, Zayed H. Involvement of Essential Signaling Cascades and Analysis of Gene Networks in Diabesity. Genes. 2020; 11(11):1256. https://doi.org/10.3390/genes11111256

Chicago/Turabian Style

S., Udhaya K., Bithia Rajan, Thirumal K. D., Anu P. V., Taghreed Abunada, Salma Younes, Sarah Okashah, Selvarajan Ethiraj, George P.D. C., and Hatem Zayed. 2020. "Involvement of Essential Signaling Cascades and Analysis of Gene Networks in Diabesity" Genes 11, no. 11: 1256. https://doi.org/10.3390/genes11111256

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